•Reviewed six meta-analyses on EIBI in children with autism including 21 studies.•Significant moderate to large effect sizes for EIBI over control group.•Parent inclusion in skill generalization ...favors increase in EIBI effectiveness.•Treatment variables impact staff-provided EIBI.•Child characteristics at intake affect parent-mediated EIBI.
This paper presents a comprehensive synthesis of six meta-analyses of early intensive behavioral interventions (EIBI) for young children with autism spectrum disorders published from 2009 to 2011. Analysis was conducted in three steps to account for different formats of treatment delivery and the extent to which parents took part in treatment. The three components of the synthesis were (a) descriptive analysis, (b) effect size analysis, and (c) mediator analysis via partial correlation and linear regressions. We completed the analysis by obtaining standardized mean difference effect sizes for 13 comparative studies ordered by comparison study type and 22 mean change effect sizes ordered by treatment delivery type. Results suggest that EIBI leads generally to positive medium-to-large effects for three available outcome measures: intellectual functioning, language skills and adaptive behaviors. Although favorable effects were apparent across comparative studies, analysis by type of delivery format revealed that EIBI programs that include parents in treatment provision are more effective. Mediator analyses suggest that treatment variables and child characteristics impact program effectiveness when accounting for the extent of parent inclusion. Clinical implications toward individualized treatment tailoring are discussed.
BACKGROUND: The relationship between early embryo post-implantation development in couples undergoing assisted reproductive techniques (ARTs) and sperm chromatin alterations has not been ...satisfactorily explained. The aim of this study was to assess the relationship between sperm DNA fragmentation in IVF/ICSI patients, sperm parameters (concentration, motility and morphology) and ART outcome, especially with regard to clinical pregnancy and pregnancy loss (spontaneous miscarriage or biochemical pregnancy). METHODS: DNA fragmentation was evaluated by TUNEL assay, performed on sperm suspensions after density gradient separation, in 132 men undergoing an ART cycle (82 IVF and 50 ICSI) and correlated with sperm parameters and ART outcome. RESULTS: A highly significant negative correlation was found between DNA fragmentation and sperm parameters. There was a close relationship between DNA fragmentation and post-implantation development in ICSI patients: the clinical pregnancy and pregnancy loss rates significantly differed between patients with high and low sperm DNA fragmentation (P = 0.007 and P = 0.009, respectively). CONCLUSIONS: Sperm DNA fragmentation seems to affect embryo post-implantation development in ICSI procedures: high sperm DNA fragmentation can compromise ‘embryo viability’, resulting in pregnancy loss.
Psychosocial stressors increase the risks for cardiovascular disease across diverse populations. However, neighborhood level resilience resources may protect against poor cardiovascular health (CVH). ...This study used data from three CVH cohorts to examine longitudinally the associations of a resilience resource, perceived neighborhood social cohesion (hereafter referred to as neighborhood social cohesion), with the American Heart Association's Life's Simple 7 (LS7), and whether psychosocial stressors modify observed relationships.
We examined neighborhood social cohesion (measured in tertiles) and LS7 in the Jackson Heart Study, Multi-Ethnic Study of Atherosclerosis, and Mediators of Atherosclerosis in South Asians Living in America study. We used repeated-measures, modified Poisson regression models to estimate the relationship between neighborhood social cohesion and LS7 (primary analysis, n = 6,086) and four biological metrics (body mass index, blood pressure, cholesterol, blood glucose; secondary analysis, n = 7,291). We assessed effect measure modification by each psychosocial stressor (e.g., low educational attainment, discrimination).
In primary analyses, adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) for ideal/intermediate versus poor CVH among high or medium (versus low) neighborhood social cohesion were 1.01 (0.97-1.05) and 1.02 (0.98-1.06), respectively. The psychosocial stressors, low education and discrimination, functioned as effect modifiers. Secondary analyses showed similar findings. Also, in the secondary analyses, there was evidence for effect modification by income.
We did not find much support for an association between neighborhood social cohesion and LS7, but did find evidence of effect modification. Some of the effect modification results operated in unexpected directions. Future studies should examine neighborhood social cohesion more comprehensively and assess for effect modification by psychosocial stressors.
We determined the efficacy and cost-effectiveness of adding an evidence-based Internet behavioral weight loss intervention alone or combined with optional group sessions to ShapeUp Rhode Island 2011 ...(SURI), a 3-month statewide wellness campaign.
We randomized participants (n = 230; body mass index = 34.3 ±6.8 kg/m(2); 84% female) to the standard SURI program (S) or to 1 of 2 enhanced programs: SURI plus Internet behavioral program (SI) or SI plus optional group sessions (SIG). The primary outcome was weight loss at the end of the 3-month program.
Weight losses differed among all 3 conditions (S: 1.1% ±0.9%; SI: 4.2% ±0.6%; SIG: 6.1% ±0.6%; Ps ≤ .04). Both SI and SIG increased the percentage of individuals who achieved a 5% weight loss (SI: 42%; SIG: 54%; S: 7%; Ps < .001). Cost per kilogram of weight loss was similar for S ($39) and SI ($35); both were lower than SIG ($114).
Although weight losses were greatest at the end of SURI with optional group sessions, the addition of an Internet behavioral program was the most cost-effective method to enhance weight losses.
Most patient-reported outcome measures (PROMs) used to assess outcomes after anatomic total shoulder arthroplasty (aTSA) focus on pain and function. Although strength is considered an important ...component of function, only the Constant-Murley score (CMS) includes an objective measurement of shoulder strength. The purpose of this study was to evaluate the relationship between shoulder elevation strength (SES) and PROMs after aTSA for the treatment of primary glenohumeral osteoarthritis (GHOA).
This was a retrospective analysis of 605 patients enrolled in a multicenter clinical database who underwent aTSA to treat primary GHOA. Patients were evaluated preoperatively and at 24 months after surgery. Outcome was assessed with the CMS, American Shoulder and Elbow Surgeons score, Western Ontario Osteoarthritis of the Shoulder score, Single Assessment Numeric Evaluation score, and patient satisfaction. Relationships between SES and outcomes were investigated.
The correlations between SES and the PROMs before and after treatment were very weak and weak, respectively (r ≤ 0.262 for all). The strength of the correlations between the absolute and adjusted CMS and the other PROMs varied from weak to moderate (r = 0.180 to r = 0.455), and the strength of the correlations was greater postoperatively. With the strength component removed from the CMS, the correlations between the CMS and other PROMs were stronger (r = 0.194 to r = 0.495).
Although measurement of SES provides objective information about shoulder function and outcome related to the treatment of primary GHOA with aTSA, the actual relevance to patients is unclear as the correlations between SES and PROMs were weak. Furthermore, the variable correlations between the CMS and PROMs call into question the exclusive use of the CMS and support the use of other PROMs that may more accurately reflect patient perception of outcome.
Mitotic spindle formation and chromosome segregation depend critically on kinetochore-microtubule (KT-MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was ...recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation.
Low adherence in recent HIV prevention clinical trials highlights the need to better understand, measure, and support product use within clinical trials. Conventional self-reported adherence ...instruments within HIV prevention trials, often relying on single-item questions, have proven ineffective. While objective adherence measures are desirable, none currently exist that apply to both active and placebo arms. Scales are composed of multiple items in the form of questions or statements that, when combined, measure a more complex construct that may not be directly observable. When psychometrically validated, such measures may better assess the multiple factors contributing to adherence/non-adherence. This study aimed to develop and psychometrically evaluate tools to screen and monitor trial participants' adherence to HIV prevention products within the context of clinical trial research.
Based on an extensive literature review and conceptual framework, we identified and refined 86 items assessing potential predictors of adherence and 48 items assessing adherence experience. A structured survey, including adherence items and other variables, was administered to former ASPIRE and Ring Study participants and similar non-trial participants (n = 709). We conducted exploratory factor analyses (EFA) to identify a reduced set of constructs and items that could be used at screening to predict potential adherence, and at follow-up to monitor and intervene on adherence. We examined associations with other variables to assess content and construct validity. The EFA of screener items resulted in a 6-factor solution with acceptable to very good internal reliability (α: .62-.84). Similar to our conceptual framework, factors represent trial-related commitment (Distrust of Research and Commitment to Research); alignment with trial requirements (Visit Adherence and Trial Incompatibility); Belief in Trial Benefits and Partner Disclosure. The EFA on monitoring items resulted in 4 Product-specific factors that represent Vaginal Ring Doubts, Vaginal Ring Benefits, Ring Removal, and Side Effects with good to very good internal reliability (α = .71-.82). Evidence of content and construct validity was found; relationship to social desirability bias was examined.
These scales are easy and inexpensive to administer, available in several languages, and are applicable regardless of randomization. Once validated prospectively, they could (1) screen for propensity to adhere, (2) target adherence support/counselling, and (3) complement biomarker measures in determining true efficacy of the experimental product.
The clinical consequences of co-infection with two or more respiratory viruses are poorly understood. We sought to determine if co-infection with pandemic 2009-2010 influenza A H1N1 (pH1N1) and ...another respiratory virus was associated with worse clinical outcomes.
A retrospective cohort study was performed of all hospitalized patients with a positive respiratory viral panel (RVP) for two or more viruses within 72 hours of admission at our institution from October 2009 to December 2009. We compared patients infected with one respiratory virus to those with respiratory viral co-infection.
We identified 617 inpatients with a positive RVP sample with a single virus and 49 inpatients with a positive RVP sample for two viruses (i.e. co-infection). Co-infected patients were significantly younger, more often had fever/chills, tachypnea, and they more often demonstrated interstitial opacities suggestive of viral pneumonia on the presenting chest radiograph (OR 7.5, 95% CI 3.4-16.5). The likelihood of death, length of stay, and requirement for intensive care unit level of care were similar in both groups, but patients with any respiratory virus co-infection were more likely to experience complications, particularly treatment for a secondary bacterial pneumonia (OR 6.8, 95% CI 3.3-14.2). Patients co-infected with pH1N1 and another respiratory virus were more likely to present with chest radiograph changes suggestive of a viral pneumonia, compared to mono-infection with pH1N1 (OR 16.9, 95% CI 4.5-62.7). By logistic regression using mono-infection with non-PH1N1 viruses as the reference group, co-infection with pH1N1 was the strongest independent predictor of treatment for a secondary bacterial pneumonia (OR 17.8, 95% CI 6.7-47.1).
Patients with viral co-infection, particularly with pH1N1, were more likely to have chest radiograph features compatible with a viral pneumonia and complications during their hospital course, particularly treatment for secondary bacterial pneumonia. Despite this, co-infection was not associated with ICU admission.
Background Cornelia de Lange syndrome (CdLS) is a rare multisystem genetic disorder which is caused by genetic defects involving the Nipped-B-like protein (NIPBL) gene in the majority of clinical ...cases (60-70%). Currently, there are no specific cures available for CdLS and clinical management is needed for life. Disease models are highly needed to find a cure. Among therapeutic possibilities are genome editing strategies based on CRISPR-Cas technology. Methods A comparative analysis was performed to test the most recent CRISPR-Cas technologies comprising base- and prime-editors which introduce modifications without DNA cleavages and compared with sequence substitution approaches through homology directed repair (HDR) induced by Cas9 nuclease activity. The HDR method that was found more efficient was applied to repair a CdLS-causing mutation in the NIPBL gene. Human-induced pluripotent stem cells (hiPSCs) derived from a CdLS patient carrying the c.5483G > A mutation in the NIPBL were modified through HDR to generate isogenic corrected clones. Results This study reports an efficient method to repair the NIPBL gene through HDR mediated by CRISPR-Cas and induced with a compound (NU7441) inhibiting non-homologous end joining (NHEJ) repair. This sequence repair method allowed the generation of isogenic wild-type hiPSCs clones with regular karyotype and preserved pluripotency. Conclusions CdLS cellular models were generated which will facilitate the investigation of the disease molecular determinants and the identification of therapeutic targets. In particular, the hiPSC-based cellular models offer the paramount advantage to study the tissue differentiation stages which are altered in the CdLS clinical development. Importantly, the hiPSCs that were generated are isogenic thus providing the most controlled experimental set up between wild-type and mutated conditions. Keywords: Cornelia de Lange Syndrome (CdLS), CRISPR-Cas9, Homology Directed Repair (HDR), Base editor, Prime editor, Patient-derived hiPSCs, Nipped-B-like protein (NIPBL), Isogenic cell line
Information about the effects of subject sampling and variable sampling on factor pattern reproduction is critical for both the design of studies and the evaluation of existing studies. This article ...reports both a review of the available literature and the results of 2 new simulation studies. Conditions investigated include the average number of variables per factor (3:1, 4:1, or 5: 1), the sample size (
N
= 50, 100, 150, 200, 400, 800)
, the method of analysis (principal component analysis, image component analysis, maximum likelihood factor analysis), pattern of loadings (equal or unequal), and the size of the average loading (.40, .60, .80). A small but consistent pattern of differences between methods occurred. Subject sample size, variable sample size, and size of the loadings can all strongly affect the degree to which a sample pattern reproduces the population pattern. The frequency of boundary cases in factor analysis is also affected by the same 3 variables. A minimum of 3 variables per factor is critical. Weaknesses in one area can be partially compensated for by strengths in another area.
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